Abstract: Objective To explore the therapeutic effect of Taohong Siwu Decoction(ThSwT on mesangial proliferative nephritis(MsPGN) in rats and examine its regulatory effect on extracellular regulated protein kinase 1/2(ERK1/2)/hypoxia inducible factor 1α(HIF-1α) signaling pathway.Methods A total of 72 Sprague-Dawley(SD) rats were randomly divided into six groups of normal control,model,low-dose(4.5 g/kg),medium-dose(9 g/kg),high-dose(18 g/kg) ThSwT and positive control(5 mg/kg of prednisone acetate) (n=12 each). Except for normal control group,another group received a subcutaneous injection of bovine serum albumin(BSA) for establishing a rat model of MsPGN. ThSwTwas delivered via gavage after successful modeling. Each group was dosed once daily for 28 daysand at24 h after the last dose. General behavior changes were observed and 24 h urinary protein was detected;the levels of creatinine(Scr) and blood urea nitrogen(BUN) were detected by enzyme-linked immunosorbent assay and the proliferation of glomerular mesangial area was observed by transmission electron microscope;Periodic acid-leuco fuchsin staining method(PAS) for observing the extracellular matrix proliferation of glomerular mesangial cells;the expressions of immunoglobulin M(IgM) and collagen IV(ColIV) detected by immunofluorescent staining;the expressions of ERK1/2 and HIF-1α by immunohistochemistry;the expressions of ERK1/2,p-ERK1/2,tissue inhibitor of metalloproteinase-1(TIMP-1),matrix metalloproteinase-9(MMP-9),tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) by Western blot.Results Compared with those in normal control group,electronic density deposition of glomerular mesangial area,glomerular epithelial cell foot swelling,glomerular basement membrane thickening and irregular arrangement were serious in model group,24 h urinary protein,Scr,BUN,IgM &Col-IV deposition and positive expressions of ERK1/2,HIF-1α,p-ERK1/2/ERK1/2,MMP-9,TNF-α and IL-6 increased(P<0.05). Compared with those in model group,electronic density deposition of glomerular mesangial area,glomerular epithelial cell foot swelling,glomerular basement membrane thickening and irregular arrangement became alleviated in low/medium/high-dose ThSwT and positive control groups,24 h urinary protein,Scr,BUN,IgM &Col-IV deposition,ERK1/2 &HIF-1α positive expression and protein expressions of p-ERK1/2/ERK1/2,MMP-9,TNF-α and IL-6 declined(P<0.05). With the incremental dose of ThSwT,the above parameters changed more significantly(P<0.05) while no significant difference existed between medium-dose ThSwT and positive control groups(P>0.05).Conclusions ThSwT may inhibit the activation of ERK1/2/HIF-1α pathway,retard the process of renal inflammation and fibrosis and improve the process of renal injury in MsPGN rats.