Abstract: Objective To study the reversal effect and mechanism of metformin on cisplatin resistant human ovarian cancer cell line SKOV3／DDP. Methods The growth inhibitory effects of cisplatin on parental group SKOV3 cell，cisplatin group SKOV3／DDP cell and combination group SKOV3／DDP cell were detected with CCK-8 assay，and the half maximal inhibitory concentration（IC50），resistance index and reversal index were calculated. Endoplasmic reticulum stress-related apoptosis related protein expressions were detected by reverse transcription-polymerase chain reaction（RT-PCR） and Western blotting method. Results SKOV3 cells and SKOV3／DDP cells were inhibited by different concentrations of metformin for 24 h，in concentration dependent manner（P＜0.05）. When metformin＞5 mmol／L， the proliferation inhibition rate of SKOV3／DDP cells was higher than that of SKOV3 cells （P＜0.05）. The IC50 of cisplatin on parental group SKOV3 cell and cisplatin group SKOV3／DDP cell and combination group SKOV3／DDP cell were 15.25 μg／ml，118.68 μg／ml and 73.45 μg／ml，respectively.The resistance index of cisplatin group SKOV3／DDP cell and combination group SKOV3／DDP cell were 7.78 and 4.81，respectively.The reversal index of metformin on the resistance of cisplatin was 1.62. The relative expression level of GRP78 mRNA of SKOV3/DDP in cisplatin group， metformin group and combination group were 0.93±0.02， 0.68±0.02， 0.49±0.07. Compared with control group （0.83±0.04）， combination group significantly decreased expression， followed by metformin group， cisplatin group was increased （P＜0.05）； the expression of GRP78 protein level was consistent with mRNA expression in each group （P＜0.05）. The expression of CHOP protein in cisplatin group， metformin group and combined medication group were 0.42±0.03， 0.69±0.03， 0.84±0.01， respectively， which were higher than that of the control group （0.39±0.05）. The difference was statistically significant （P＜0.05）. Conclusion Metformin may regulate the cisplatin-resistance in ovarian carcinoma by endoplasmic reticulum stress （ERS）， in which metformin decrease the expression of GRP78 and increase the expression of CHOP.