Objective To investigate the activation and role of signal transduction pathway of epidermal growth factor (EGF)-epidermal growth factor receptor (EGFR)-mitogen activated protein kinase (MAPK) in proliferation of human retinal pigment epithelial (RPE) cells. Methods Human RPE cells were stimulated with 0.1%，10% foetal calfserum (FCS) and EGF(0.1, 1, 10, 50 and 100 ng/ml)in 0.1% FCS Dulbeco′s modified Eagle′s medium (DMEM) and in 10% FCS DMEM for 3 days, respectively. Immunohistochemical staining and in situ hybridization were used to observe the expressions of EGFR protein and EGFR mRNA，respectively. Activation of MAPK was detected by immunohistochemical method with specific anti-phosphorylated ERK 1/2 antibody. Results The optimal concentrations of EGF were 10 ng/ml in 0.1% FCS DMEM and 1 ng/ml in 10% FCS DMEM. After 3 days of stimulation with EGF, phosphorylated ERK 1/2 staining was detectable in nucleus of RPE cells, whereas cells presented immunostaining for phosphorylated ERK 1/2 in the cytoplasm before stimulation. Conclusions EGF may improve the expression of EGFR protein and EGFR mRNA of RPE cells, and induced MAPK nuclear translocation in a concentration-dependent manner. EGF-EGFR-MAPK signal transduction pathway may play a key role in RPE cells proliferation, and serum exerts an important acceclerating function in the process. (Chin J Ocul Fundus Dis，2004，20：67-132)