Abstract: Objective　To investigate the effect of high uric acid on cardiomyocyte activity in vitro and its related mechanism. Methods　H9C2 cells were divided into the control group (Con), the high uric acid group (HUA), the antioxidant group (NAC), the ERK inhibitor group (PD98059), the P38 inhibitor group (SB203580), the high uric acid + antioxidant group (NAC+HUA), the high uric acid + ERK inhibitor group (PD98059+HUA), the high uric acid + P38 inhibitor group (SB203580+HUA) and the high uric acid + antioxidant + ERK inhibitor group (NAC+PD98059+HUA). MTT method was used to detect the vitality of cardiomyocytes. Immunofluorescence staining and flow cytometry were used to detect the reactive oxygen species (ROS). Western blot assay was used to detect the protein expression levels of extracellular signal regulating kinase (ERK) and phosphorylated P38. Results　After treatment with high uric acid (0.15 g/L), the activity of cardiomyocytes decreased significantly. Compared with the Con group, the oxidative pressure increased significantly in the HUA group, while compared with the HUA group, the oxidative pressure decreased in the NAC+HUA group (P＜0.05). Compared with Con group, the activity level of cardiomyocytes decreased significantly in the HUA group, while compared with the HUA group, the activity levels of cardiomyocytes increased significantly in the NAC+HUA group, PD98059+HUA group and SB203580+HUA group (P＜0.05). Compared with the Con group, phosphorylation levels of ERK and P38 were increased significantly in HUA group. Compared with the HUA group, the phosphorylation levels of P38 of SB203580 group were decreased significantly, while the phosphorylation levels of ERK and P38 were decreased significantly in NAC+HUA group, PD98059+HUA group and NAC+PD98059+HUA group (P＜0.05). Conclusion　High uric acid inhibits myocardial cell activity by activating ERK/P38 signaling pathway through oxidative stress in vitro.