Objective To explore the effect of a certain dose of endotoxin， lipopolysaccharide （LPS） on skull repair in rats and the role of alendronate sodium （ALN） in improving skull repair. Methods Twenty SD male rats were randomly divided into blank， control， LPS and LPS+ALN groups to establish an animal model of LPS-induced and LPS-combined ALN for skull defect repair. Microscopic computed tomography （Micro-CT） was used to observe the skull repair in rats， enzyme-linked immunosorbent assay （ELSIA） was used to detect the levels of three inflammatory factors， namely interleukin-1β （IL-1β）， interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α）， in the blood of rats， and hematoxylin-eosin （HE） staining was utilized to observe the bone structure and cells. The status of osteoclasts at the skull defect was examined using tartrate resistant acid phosphatase （TRAP） staining of sections， and the mechanism of bone growth and bone resorption was investigated using immunohistochemistry. Results The results of the tested factors showed that， compared with blank group or control group， LPS caused abnormal expression of erythrocytes， hemoglobin， and platelets with a statistical difference （P＜ 0.05）， and there were statistically significant differences in inflammatory factors such as IL-1β （P=0.014）， IL-6 （P=0.049）， and TNF-α （P=0.006） after ALN administration. Compared with blank group， Micro-CT showed that significant bone resorption occurred in control group， LPS group， and LPS+ALN group， but significant intercranial resorption occurred in LPS group on day 2， while resorption was suppressed after ALN treatment. （3） Analyzing the pathological results， LPS led to an increase in osteoclasts， causing bone loss and bone structure defects， and significant bone resorption occurred in the skull， while less bone resorption occurred in LPS+ALN group， and the markers of osteoclast differentiation， osteocalcin and transforming growth factor-β， were least expressed at 46 days， with a higher rate of repair than in the other groups. Conclusions LPS immersion triggers bone resorption， which is detrimental to the proliferation and differentiation of rat skull osteoblasts， and ALN treatment effectively accelerates osteogenesis and inhibits the inflammatory bone resorption caused by LPS， thus improving the skull repair.