OBJECTIVE: To find out the critical influential factors of measurement in the determination of Roxithromycin dispersible tablets. METHODS: Mathematic model of HPLC was established to analyze the effects of many uncertain factors on measurement results. Combined standard uncertainty and expanded standard uncertainty were calculated. RESULTS: The expanded uncertainty was 1.6% and the results of determination could be expressed as (96.8?1.6)%. CONCLUSION: The established analytical method is applicable to the uncertainty analysis in the content determination of Roxithromycin dispersible tablets by HPLC.