Abstract: Objective To explore the expression of P38 MAPK signaling pathway and uPA in ovarian cancer and related clinical significance. Methods The expression of uPA, AKT, ERK and P38MAPK were detected in 49 cases of ovarian cancer tissues by immunohistochemistry. The expression of uPA and P38MAPK were detected by Western blot in ovarian cancer cell lines HO8910 and HO-8910PM. We detected the change ofuPA protein expression after P38MAPK signal pathway was cut off by SB203580 specific inhibitor. Results Immunohistochemical method results showed that the positive expression rates of uPA, P38MAPK, ERK and AKT protein were 61.22%, 57.14%, 53.06% and 55.10%, respectively. The expression of uPA was positively correlated with P38MAPK(r=0.8645, P=0.001), and was related with clinicopathologic stage, differentiated degree, lymph node metastasis(all P<0.05), but not related with age or histologic type(P>0.05). The expression of AKT and ERK were related with lymph node metastasis and greater omentum metastasis(P<0.05), but not related with age, histologic type or clinicopathologic stage(P>0.05). The expression of uPA in HO-8910PM cell line was higher than that in ovarian cancer cell lines HO8910, and the expression of uPA was decreased when P38MAPK signal pathway was cut off by SB203580, in a concentration-dependent manner.The expression of P38MAPK and uPA were significantly correlated to the prognosis of ovarian cancer patients(r=3.897, 11.044, P=0.048, 0.001). Conclusion P38MAPK signal pathway is activated in ovarian cancer tissues. The activated p38MAPK signal pathway could upregulate the expression of uPA, which may contribute to the development of ovarian cancer. P38MAPK signal pathway and uPA may play an important role in the invasion and metastasis of ovarian cancer. P38MAPK and uPA might help to evaluate the prognosis of ovarian cancer patients.