Objective To understand the effect of astaxanthin on intestinal injury of septic mice, and explore the mechanism. Methods Septic mice model was constructed by cecum ligation and puncture (CLP). Sixty-two male Balb/c mice were randomly divided into 4 groups by random number method: Sham surgery+solvent control group (Sham+Vehi group, n=11), Sham surgery+astaxanthin group (Sham+Asta group, n=11), sepsis model+solvent control group (CLP+Vehi group, n=20), and sepsis model+astaxanthin group (CLP+Asta group, n=20). In astaxanthin-containing groups, astaxanthin was dissolved in edible olive oil (40 mg/mL), and 100 mg/(kg·d) was gavaged for 7 days before surgery. In solvent-containing groups, the solvent was treated with an equal amount of olive oil by gavage (2.5 mL/kg). Five mice from the Sham groups and 12 mice from the CLP groups were randomly selected to observe their 7-day survival after surgery. The remaining mice were given fluorescent isothiocyanate dextran (FD-40) gavage at 18 hours after surgery. Changes in mice intestinal tissue morphology, intestinal functional injury indicators, intestinal tissue oxidative stress indicators, inflammatory factors expression, and expression of key protein of peroxisome proliferator-activated receptor γ (PPARγ)/nuclear factor kappa B (NF-κB) were detected 24 hours after surgery. Results There were no statistical differences in mice survival rate, intestinal injury indicators, intestinal inflammatory factor levels, oxidative stress indicators, and intestinal tissue injury scores between Sham+Vehi and Sham+Asta groups (all P>0.05). Compared with the Sham+Vehi group, the survival rate of mice in the CLP+Vehi group decreased significantly; serum diamine oxidase (DAO) activities, levels of intestinal fatty acid binding protein (I-FABP), D-lactate, and FD-40 increased significantly; levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and malondialdehyde (MDA) in intestinal tissue increased significantly; superoxide dismutase (SOD) activity decreased; intestinal morphological injury score was higher; the expression of PPARγ in intestinal tissue increased, and the ratios of both p-IκBα/IκBα and p-p65/p65 increased (all P < 0.05). Compared with the CLP+Vehi group, the survival rate of mice in the CLP+Asta group improved; serum DAO activities, levels of I-FABP, D-lactate and FD-40 all decreased significantly; levels of TNF-α, IL-1β, IL-6 and MDA in intestinal tissue decreased significantly; SOD activity increased; intestinal morphological injury score decreased; PPARγ expression in intestinal tissue increased, and the ratios of both p-IκBα/IκBα and p-p65/p65 decreased (all P < 0.05). Conclusion Astaxanthin decreases intestinal injury in CLP-induced septic mice, and its mechanism may be related to the regulation of PPARγ/NF-κB signaling pathway, as well as the inhibition of inflammatory response and oxidative stress.