Objective: To investigate the effect of circ_0010729 on high glucose-induced mesangial cell injury. Methods: Human glomerular mesangial cells HMCL were divided into a control group, a high glucose (HG) group, a HG + miR-NC group, a HG + miR-654-3p group, a HG + si-NC group, a HG+si-circ_0010729 group, a HG + si-circ_0010729 + anti-miR-NC group, and a HG + si-circ_0010729 + anti-miR-654-3p group. Real-time PCR was performed to detect the expression levels of miR-654-3p and circ_0010729; flow cytometry was performed to detect the apoptosis of glomerular mesangial cells; ELISA was performed to detect interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels; dual luciferase report experiment was used to verify the targeting relationship between circ_0010729 and miR-654-3p. Results: Compared with the control group, the circ_0010729 expression was increased, the miR-654-3p expression was decreased, the apoptosis rate was increased, the TNF-α and IL-6 levels were increased in the HG group (P<0.05). After inhibiting the expression of circ_0010729 or overexpression of miR-654-3p, the apoptosis rate of human glomerular mesangial cells induced by high glucose was decreased, the levels of TNF-α and IL-6 were decreased (P<0.05). circ_0010729 targeted and regulated miR-654-3p; interfering with the expression of miR-654-3p reversed the effect of inhibiting the expression of circ_0010729 on the apoptosis and inflammation of human glomerular mesangial cells induced by high glucose. Conclusion: Inhibiting the expression of circ_0010729 may inhibit the apoptosis and inflammation of glomerular mesangial cells induced by high glucose through targeting up-regulation of miR-654-3p expression.