Objective To investigate the effects of ultrasound with different parameters on lipopolysaccharide (LPS)-induced human mesangial cell (HMC) proliferation so as to provide the experimental data for ultrasound combined with microbubbles or drug in glomerulonephritis therapy. Methods HMC proliferation model induced by 10μg/mL of LPS was used to determine the effects of ultrasound with different parameters on cellular proliferation. (1) Based on three ultrasonic factors including the intensity (1.48W/cm2, 2.56W/cm2 and 2.79W/cm2), duty cycle (1:4, 1:1 and 4:1) and exposure time (5min, 10min and 15min), nine experimental groups were respectively designed by orthogonal methods in LPS-induced HMC proliferation model with different ultrasonic treatments as well as the control group (without any treatment) and the model group (treated by LPS alone) were designed. (2) We also examined the effects of ultrasound with different intensity (2.17W/cm2, 2.56W/cm2 and 2.79W/cm2) and exposure time (5min and 10min) at a 1:1 duty cycle on LPS-induced HMC proliferation. Besides cellular morphology, their growth inhibition rates were evaluated by MTT assay and these three parameters were in turn analyzed in both experiments. Results Range and variance analysis showed that three ultrasonic parameters had inhibitory effects on cellular viability in LPS-induced HMCs, but the duty cycle of the ultrasound was the most important factor. Inhibition on cell growth was not significantly observed in the experimental groups at the duty cycle of 1:4. However, the cell growth inhibition rates were more than 60.00% in the three experimental groups at the duty cycle of 4:1. Moreover, the inhibitory effects of ultrasound with different intensity and exposure time at a 1:1 duty cycle were different on LPS-induced HMC proliferation. Conclusion Ultrasound with different parameters has different effects on LPS-induced HMC growth inhibition, but the duty cycle of the ultrasound is the most important ultrasound factor affecting cell growth inhibition in vitro.