Background: The SF-36 is widely used as a significant health outcome or quality of life indicator and validated in many languages versions including Chinese. But the Chinese version of the SF-36 (CSF-36) is rarely used for those patients with hypertension, coronary heart diseases, chronic gastritis and peptic ulcer in China. Therefore, the CSF-36 needs to be validated in patients with chronic diseases. Objectives: This paper is aimed to validate the CSF-36 using an in-patient sample of four chronic diseases from mainland China, with focusing on psychometric properties. Methods: The CSF-36 was used in a longitudinal study consisting of 534 patients in these four chronic disease groups. The psychometric properties of the scale were evaluated by indicators such as validity and reliability coefficients Cronbach a, Pearson r, standardized response mean employing correlational analyses, multi-trait scaling analysis, t-tests, factor analyses and structural equation models. Results: Testretest reliability coefficients for all domains were higher than 0.80 with a range of 0.83 to 0.96; the internal consistency (a) for most domains was higher than 0.70. Five of the eight domains as well as the Physical and Mental Health subscale summaries all had statistically significant changes after treatment with the SRM ranging from 0.18 to 0.28. Conclusion: The CSF-36 showed good validity and reliability but small responsiveness when used in patients. It is a good and useful instrument for patients with chronic disease at some situations.