Objective To explore the effects of Zhu Ling decoction and Alisma orientalis on the osteopotin mRNA expression in the experimental rat model of renal stone. Methods The experimental rat model of renal stone was set up using glyoxylic acid. Osteopontin mRNA expression in the renal tissues in the experimental rat model of renal stone was detected by RT-PCR. Results Glyoxylic acid obviously increased osteopontin mRNA expression in the renal tissues. Zhu Ling decoction and Alisma orientalis remarkably decreased the expression of osteopontin mRNA in the renal tissues. Conclusion Zhu Ling decoction and Alisma orientalis could decrease the osteopotin mRNA expression in the renal tissues in the experimental rat model of renal stone. The results were helpful for prevention and treatment of renal stone.