OBJECTIVE: To study effects of different pH values on physicochemical property and in vitro transdermal parameters of indomethacin. METHODS: HPLC method was used for quantitative analysis; solubility, apparent partition coefficient (Kapp) and in vitro transdermal parameters [permeation rate (Js) and 4, 12, 24 h accumulative premeation amount (Q4 h, Q12 h, Q24 h)] of Indomethacin gel were determined at pH 5.0, 5.8, 6.5, 7.3, 8.0. The multiple correlation analysis and regression model were used to determine the correlations of pH, solubility, Kapp and transdermal parameters. RESULTS: Indomethacin gel in vitro transdermal model fully complied with zero-order kinetic model; and pH was good linear relationship with solubility and Kapp (r≥0.892 0), showing good correlation (r≥0.968 0); the exponential model relationships were shown among pH, solubility, Kapp and in vitro transdermal parameters; using pH 7.3 as the critical point, corresponding Kapp was equal to 3.34. CONCLUSIONS: Adjusting pH can improve the solubility and Kapp of indomethacin; adjusting existing form of molecular ion can increase Q and Js of indomethacin.