Objective To observe the protective effects of roscovitine on the podocyte injury induced by endoplasmic reticulum stress (ERS) caused by tunicamycin. Methods The differentiated podocytes cultured at 37℃were randomly di-vided into:(1) Control group, DMSO group and tunicamycin group (TM, 1.0μmol/L). The treatment was given for 3, 6 and 12 hours in three groups. (2) For control group, tunicamycin group, tunicamycin+roscovitine group (20, 40μmol/L, TM+ROS), the treatment was given for 12 hours. The podocyte apoptosis was detected by flow cytometry and TUNEL method. The ex-pressions of Cdk5, GRP78, Caspase-12 and CHOP were detected by Western blot assay. Results (1) Compared with con-trol group and DMSO group, the podocyte apoptosis was increased significantly in a time dependent manner after tunicamy-cin treatment in TM group;the protein expressions of Cdk5, GRP78, Caspase-12 and CHOP were also up-regulated signifi-cantly in TM group (P<0.05). (2) Flow cytometry and TUNEL analysis showed that tunicamycin induced apoptosis in podo-cytes, which was significantly inhibited by roscovitine in a concentration dependent manner in TM+ROS group as compared to that of TM group (P<0.05). The protein expressions of GRP78, Caspase-12 and CHOP were also significantly decreased in a concentration dependent manner in TM+ROS group compared to those of TM group (P<0.05). Conclusion Roscovi-tine, the inhibitor of Cdk5, can reduce the podocyte apoptosis induced by tunicamycin. The protective effects of roscovitine on podocytes can be a novel approach of treating diabetic nephropathy.