BACKGROUND: Along with global climate change, the relationship between temperature variability (TV) and cardiovascular hospitalization and deaths have been well established. However, limited studies were conducted to reveal the underlying mechanism for TV-related cardiovascular diseases. OBJECTIVES: In the current study, a novel TV calculation, taking account for both interday and intraday TV as well as lag effects, was used to investigate the effect of short-term TV on the level of high-sensitivity C reactive protein (hs-CRP), which is a crucial preclinical predictor for cardiovascular disease (CVD). RESULTS: Among the 11,623 Chinese population (46.0% male; mean age 49.8Êyears), the average hs-CRP was 1.4Êmg/ L (standard deviation 1.6Êmg/L). Statistical significance between TV and hs-CRP was observed for different TV exposure days (TV01-TV07) in adjusted model, with highest effect for TV06. Specifically, per 1Ê¡C increase in TV06 led to 2.241% (95%CI: 1.552%-2.935%) increase in hs-CRP. Female, obesity and elderly population were more susceptible to TV. The largest mediator for the association of TV and hs-CRP was lipoprotein(a), accounting for 8.68%, followed by smoking status (4.78%), alcohol use (3.95%) and systolic BP (3.20%). CONCLUSION: Short-term TV will significantly increase the level of hs-CRP, suggesting hs-CRP to be the potential biologic mechanisms underlying the cardiovascular effects of TV. And more attention should be paid to unstable weather in the global climate change context. Further developing efficient public health policies on climate change may benefit for global heath.