AIM: To identify the key factors responsible for drug resistance in different ovarian cancer cell lines using protein microarray system. METHODS: Six ovarian cancer cell lines were employed. The sensitivity of ovarian cancer cell line to common chemotherapeutic drugs was determined by using MTT assays. The expression of 78 cytokines and other factors was examined by using cytokine antibody array technology. RESULTS: Different ovarian cancer cell line responded to chemotherapeutic agents differently. The drug resistance was correlated with certain cytokine expression. Cell line SKOV3 was less sensitive to first line chemotherapeutic drug (ADM, CBPDA) and accumulated high amounts of GRO and TIMP-2 compared with other 5 cell lines. OVCAR4 cells were more resistant to second line chemotherapeutic drug (TAXOL, VP16) and had higher levers of IL-6 and IL-8 than IGROV1, OVCAR3 and OVCAR5. CONCLUSIONS: Among the most common excretive cytokines, increasing of GRO, IL-6, IL-8 and TIMP-2 might be related to drug-resistance of ADM and CBPDA in ovarian cancer cell, while IL-6 and IL-8 might also be related with drug resistance of TAXOL and VP16. The different types of ovarian cancer cell might have roughly similar excretive cytokines-induced mechanism of drug resistance.