Objective:To investigate the activity and possible role of MAPK in mesangial cells in response to high glucose and to research the mechanism of diabetes nephopathy. Methods:The human mesangial cells were cultured and stimulated by high glucose.The MAPK activity was measured by liquid scintilation counting. Production of fibronectin was analyzed by ELISA. The expression of c-fos was assayed by immunochemistry. Results: Compared with the control glucose, high glucose increased the activity of MAPK, the expression of c-fos and the production of FN. When PD98059 were used, these three all decreased. Conclusion: High glucose can active MAPK, increase the expression of c-fos and the production of FN and contribute to diabetes nephopathy.