Objective To investigate the expression changes of A1/A2 astrocytes over time after diffuse brain injury （DBI） in the hippocampus of mice. Methods A total of 48 male SD mice were randomly divided into normal control group and 4 h， 8 h， 12 h， 1 d， 3 d， 5 d， 7 d group after DBI （n=6）. The DBI model was established by modified Marmarou brain injury strike device. Brain injury in mice was observed by gross observation and hematoxylin-eosin （HE） staining. The expression of C3d， S100A10 and their mRNA， the markers of A1/A2 astrocytes （A1s/A2s） in the hippocampus of mice were detected by immunohistochemical staining and real-time quantitative Polyerase Chain Reaction （PCR）. Results Gross observation showed that there was no obvious abnormality in the normal control group， but there were localized subarachnoid hemorrhage， a small amount of hemorrhage in the lateral ventricle and ventral side of brain tissue， mild edema and no focal brain contusion and laceration in the experimental group. The results of HE staining showed that the morphological changes of cerebral cortex and deep brain tissue in the experimental group after DBI， and the craniocerebral injury of mice was diffuse. DBI model was successfully established. The results of immunohistochemical staining showed that the mean density of C3d protein in the hippocampus of the normal control groupmice was （0.002 6±0.000 3）. It increased to （0.003 4±0.000 1） at 4 h after DBI， and reached a peak of （0.015 8± 0.000 4） at about 1 d after DBI. The staining was significantly deepened， and then the mean density gradually decreased. It was still higher than that in the normal control group at 7 d after DBI， the mean density was （0.003 6± 0.000 2）. The mean density of C3d protein in the hippocampus of 8 h， 12 h， 1 d， 3 d and 5 d after DBI were all higher than that in the normal control group， and the differences were statistically significant （P ＜ 0.05）. The mean density of S100A10 protein in the hippocampus of the normal control group mice was （0.078 7±0.006 8）， which decreased to （0.051 9±0.002 1） at 4 h after DBI， and was the lowest at 1d， reaching （0.005 2±0.000 2）， then showing an upward trend， （0.034 6±0.001 8） at 7 d. The mean density of S100A10 protein in hippocampus of mice in groups 4 h， 8 h， 12 h， 1 d， 3 d， 5 d and 7 d after DBI was lower than that in the normal control group， and the difference was statistically significant （P＜0.05）. The results of real-time fluorescent quantitative PCR showed that C3d increased at 4 h after DBI and peaked at 8 h with the relative expression （9.365 2± 0.543 8） 2-Δ △ Ct， then decreased gradually. S100A10 began to decrease at 4 h after DBI， and its expression level was the lowest around 8 h， with the expression level of （0.446 9±0.007 8） 2-Δ △ Ct， followed by an upward trend. The C3d mRNA expression of mice in the groups 4 h， 8 h， 12 h， 1 d， 3 d， 5 d and 7 d after DBI was higher than that in the normalcontrol group， and the S100A10 mRNA expression of mice in the groups 4 h， 8 h， 3 d， 5 d and 7 d after DBI was lower than that in the normal control group， with statistical significance （P＜ 0.05）. Conclusions Within 7 days after DBI， A1s and A2s showed unimodal expression， and the trend was opposite， which is expected to become a biological index for estimation of injury time and treatment of DBI， and provide a theoretical basis for clinical medication and treatment.