Resveratrol, a natural antioxidant, anti-inflammatory plant extract, was found to have a protective effect in poultry subjected to heat stress. In this study, we strove to characterize resveratrol on intestinal of duck exposed to acute heat stress and investigate the underlying mechanism. A total of 120 Shan-ma ducks (60 days old) were randomly divided into 2 groups. The control group was fed a basal diet, and the resveratrol group was fed a basal diet supplemented with 400 mg/kg resveratrol. Animals in 2 groups were kept at a temperature of 24°C ± 2°C for 15 d. Then, animals of both groups were placed in an artificial climate room at 39°C. Twelve ducks of each group were sacrificed for sampling at 0, 30, and 60 min, respectively. Results indicated that resveratrol increased the ratio of villus height to crypt depth, increased the number of goblet cells, and reduced the histopathological damage of jejunum caused by acute heat stress. Furthermore, the gene expression of heat shock proteins (
HSP60, HSP70
, and
HSP90
) and tight junction proteins (
CLDN1
and
OCLN
) was significantly increased in the resveratrol group compared to that in the control groups. Simultaneously, resveratrol significantly activated the
SIRT1-NRF1/NRF2
signaling pathways, improved ATP level of jejunum, and increased SOD and CAT antioxidant enzymes activities. In addition, we found that the
NF-κB
/
NLRP3
inflammasome signaling pathways were repressed under acute heat stress. Meanwhile, supplement resveratrol further inhibited the
NLRP3
inflammasome pathway, decreased protein level of
NLRP3
and caspase1 p20, reduced the secretion of IL-1β. Taken together, our results indicate that resveratrol against the oxidative damage and inflammation injury in duck jejunum induced by heat stress via active
SIRT1
signaling pathways.