Objective To investigate the effect of repetitive transcranial magnetic stimulation (rTMS) on cognitive impairment and the expression of endocannabinoid system-related genes, including CB1R (cannabinoid receptor1), DAGLα (Diacylglycerol-α), NAPE-PLD (N acylphosphatidyl ethanolamine phospholipase D), FAAH (Fatty acid amide hydrolase) and MAGL (monoacylglycerol) in the hippocampus in cuprizone (CPZ)-induced mice model of schizophrenia. Methods A total of 24 C57BL/6 mice were randomly assigned to the following 3 groups (n=8 for each group): sham, CPZ and CPZ + rTMS. The mice in the CPZ + rTMS and CPZ group were administered 0.2% CPZ in standard powdered rodent chow for 6 weeks, then received rTMS treatment (5 Hz, 1.26T) or sham rTMS treatment for 7 days; concurrently, the mice in sham group were fed with normal powdered rodent chow for 6 weeks, and then received sham rTMS treatment for 7 days. 24 hours after the completion of the last rTMS intervention, mice were subjected to Y-maze and 3-chamber tests. Then the mice were sacrificed, and Western blot was used to detect the protein expression of cannabinoid related genes in hippocampus. Results Compared with sham group, CPZ group showed significant spatial memory impairment and social deficits, including decreased percentages of spontaneous alternations in Y maze test [sham (62.69±7.92)% vs CPZ (43.78±14.30)%, P < 0.01], and less duration with stranger in the 3-chamber test [sham: (233.41±3.84) vs (157.02±63.62), P<0.05); CPZ: (164.30±79.16) vs (249.28±58.31) s,P< 0.05)]. Compared with sham group, the expression levels of CB1R, DAGLα and NAPE-PLD in hippocampus of the CPZ group was decreased [(1.14±0.09) vs (0.77±0.13), (0.76±0.12) vs (0.38±0.10), (0.81±0.12) vs (0.36±0.11), P < 0.05], while expression of FAAH of the CPZ group was increased [(0.73±0.09) vs (1.14±0.16), P < 0.05]. rTMS treatment improved cognitive impairment and social deficits in mice exposed to CPZ, evidenced by increased percentages of spontaneous alternations in Y maze test in CPZ+rTMS group than in CPZ group [CPZ: (43.78±14.30)% vs CPZ+rTMS: (60.40±10.62)%, P< 0.05], and more duration with stranger in the 3-chamber test [(236.74±51.66) vs (158.41±68.45) s, P< 0.05]. rTMS treatment reversed the level of endocannabinoid system-related genes in the hippocampus of CPZ mice, since the differences of the expression levels of CB1R, DAGLα and NAPE-PLD in hippocampus between CPZ+rTMS group [(1.13±0.11), (0.68±0.13), (0.66±0.08), (0.64±0.14)] and CPZ group were statistically significant (P < 0.05). Conclusions rTMS treatment can improve the cognitive impairment in CPZ-induced schizophrenia mice model and restored the protein level of endocannabinoid system-related genes in the hippocampus.