Objective To investigate the protective effect of curcumin pretreatment on the intestinal mucosa in rats in dry and hot desert environment. Methods Eighty male SPF grade rats were randomly divided into saline control group (NC group) and curcumin pretreatment group (HDC group) (40 in each group). Rats in the NC group were gavaged with saline, and rats in the HDC group were gavaged with curcumin (200 mg/kg), once a day for 7days. The rats were placed in a cabin simulating the dry and hot desert environment (41±0.5)℃ and relative humidity of (10±2)%. Rats were randomly taken from each groups (n=10) and sacrificed with 3% sodium pentobarbital intraperitoneally at 0 min, 50 min, 100 min and 150 min time points. The ileal tissue was stained for histological examination and oxidative stress index was detected. Results At time points 0 min and 50 min, the pathological injury scores of the HDC group were not significantly different compared with the NC group (P > 0.05). At time points 100 min and 150 min, the pathological injury scores of the HDC group were significantly decreased compared with the NC group (P < 0.01). At time points 50 min, 100 min and 150 min, the CAT and SOD activity of HDC group were significantly increased compared with the NC group (P< 0.05 or P< 0.01). The MDA content of HDC group were significantly decreased compared with the NC group (P< 0.05 or P< 0.01). Exposed to dry and hot environment, the pathological injury scores of the NC group were negatively correlated with CAT and SOD activity (r=-0.9128, r=-0.9125, P< 0.01), and positively correlated with MDA content (r=0.9258, P< 0.01). Conclusions Curcumin pretreatment can protect the intestinal mucosa of rats in dry-heat environment of desert, and curcumin can alleviate the pathological damages of intestinal mucosa by inhibiting the oxidative stress in intestinal mucosa.