Objective To investigate the effect of PARP inhibitor 3?aminobenzamide(3?AB)on cortical neurons in streptozotocin?induced diabe?tes mellitus(DM)rats and the mechanism. Methods A total of 60 rats were divided into 3 groups randomly:sham?operated control group,DM group and DM+3?AB group,20 rats in each group. Morris maze was used to detect learning and memory abilities in each group. Spectrophotometer assay was used to detect the levels of superoxide dismutase(SOD),glutathione peroxidase(GSH?Px)and malondialdehyde(MDA)in cortex. West?ern blot was used to determine the expression of poly(ADP?ribose)polymerase 1(PARP1)in cortex. Immunohistochemical staining was used to de?termine the expression of caspase?3?immunoreactive neurons in cortex. Results DM rats showed significantly declined learning and memory abili?ties. Compared with the control group,the levels of SOD and GSH?Px were significantly reduced(P<0.01)and the level of MDA was significantly up?regulated(P<0.01)in the DM group. Compared with the DM group,the levels of SOD and GSH?Px were significantly higher(P<0.05)and the level of MDA was significantly lower in the DM+3?AB group(P<0.05). The expression level of PARP1 was significantly up?regulated in the DM group and was significantly decreased in the DM+3?AB group(P<0.01). The level of caspase?3 was significantly higher in the DM group than in the control group(P<0.01),and was significantly decreased in the DM+3?AB group(P<0.01). Conclusion 3?AB protected cortical neurons from apoptosis in DM rats by inhibition of PARP1 and alleviation of oxidative stress.