Objective To investigate the effect of glycyrrhizic acid (GA) on the inflammatory and fibrotic factors in high glucose-induced glomerular mesangial cells (SV40 MES13). Methods Cultured mouse SV40 MES13 were divided into normal group (NG, 5.6 mmol/L glucose), high glucose group (30 mmol/L glucose) and HG+GA group (30 mmol/L glucose+200 μmol/L GA). The expression levels of inflammatory cytokines interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), IL-6, IL-8 and α-smooth muscle actin (α-SMA) in different groups were detected by Western blotting. The fluorescence intensity of IL-1β, TNF-α and α-SMA in different groups were detected by immunofluorescence. The levels of IL-1β, TNF-α, IL-6 and IL-8 in the culture supernatant of different populations were detected by enzyme-linked immunosorbent assay (ELISA). Results The protein expressions of IL-1β, TNF-α, IL-6, IL-8 and α-SMA in HG group were significantly higher than those in NG group (P<0.01); Compared with HG group, the protein expression levels of IL-1β, TNF-α, IL-6, IL-8 and α-SMA decreased significantly in HG+GA group (P<0.05). The fluorescence intensity of inflammatory cytokines IL-1β, TNF-α and α-SMA increased in HG group than those in NG group (P<0.05); While compared with the HG group, the fluorescence intensity of IL-1β, TNF-α and α-SMA in HG+GA group decreased markedly (P<0.05). The experimental results of ELISA showed that compared with NG group, the levels of IL-1β, IL-6, TNF-α and IL-8 in cell supernatent increased in HG group (P<0.01); while the levels of IL-1β, TNF-α, IL-6, IL-8 in HG+GA group significantly lower than those in HG group (P<0.05). Conclusion Glycyrrhizic acid has certain inhibitory effect on high glucose-induced inflammatory factors and fibrotic factors in glomerular mesangial cells, which may play an important role in prevention of diabetic nephropathy.