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Background Secreted protein acidic and rich in cysteine (SPARC) may play a role in the prevention of colon cancer through exercise, while SPARC is considered as a promoter of insulin resistance. The purpose of the present study was to clarify the effects of replacing sedentary time with either light-intensity PA (LPA) or moderate- to vigorous-intensity PA (MVPA) on serum SPARC in a general population. Methods The study subjects were 4000 men and 6040 women (40 to 69 years) who participated in baseline surveys of a population-based cohort study. Sedentary time, LPA, and MVPA were objectively measured by an accelerometer. The serum SPARC concentration was measured by an enzyme-linked immunosorbent assay. Using an isotemporal substitution model, cross-sectional associations of replacing sedentary time with either LPA or MVPA on serum SPARC levels were analyzed according to sex. Adjustment was made for potential confounding factors. Results In men, replacing 60 min of sedentary time with 60 min of MVPA was associated with 23 ng/mL (confidence interval -43, -2) lower serum SPARC levels even after adjusting for confounders, including the BMI (P = 0.028), while no such association was observed for LPA. Furthermore, no such significant replacement effects were observed in women. Conclusions The current study showed that replacing sedentary time with MVPA results in reduced serum SPARC concentrations in men. Key messages Effect of habitual PA to decrease circulating SPARC is PA intensity-specific. [ABSTRACT FROM AUTHOR]