Abstract: To investigate the effect of estrogen receptor(ER)agonist 17β-estradiol and G protein-coupled estrogen receptor 1(GPER)agonist fulvestrant on masangial cell fibrogenesis under protein kinase C(PKC), we quantified type IV collagen(COL4A1), fibronectin(FN1), connective tissue growth factor(CTGF)and transforming growth factor-β1(TGFβ1)gene transcription and semi-quantified phosphorylation of Akt signal upon Phorbol 12-myristate 13-acetate stimulation(which increased COL4A1, FN1, CTGF and TGFβ1 gene transcription to 2. 5±0. 5, 1. 4±0. 2, 26±11 and 1. 9±0. 3 times compared with baseline, P< 0. 05)when incubated with the two drugs. It was found that 17β-estradiol and fulvestrant down-regulated COL4A1, FN1, CTGF and TGFβ1 genes transcription(P< 0. 05)and Akt signaling under PKC activation via ER and GPER. ER and GPER agonists are beneficial in protecting the mesangial cells from fibrogenic stimuli by inhibiting PKC signaling and excessive extracellular matrix production.