Aim To explore the effect and mechanism of astaxanthin on cerebral infarction rats based on AMPK/eNOS/NF-kappa B signal pathway. Methods The rat model of cerebral infarction was established by modified Longa method. 50 successful modeling SD male rats were randomly divided into model control group, positive control group, astaxanthin low, medium and high dose group, with 10 rats in each group, and 10 rats without model as blank control group. The blank control group and the model control group were given the same volume of normal saline, the positive control group was given 20 mg/(kg·d) nimodipine, and the astaxanthin low, medium and high dose groups were given 0,0, 30 mg/(kg·d) astaxanthin, respectively, for 14 consecutive days. Neurological changes were detected in rats; cerebral infarction area was measured by triphenyl tetrazolium chloride staining; levels of interleukin-10 (IL-10), interleukin-1β, interleukin-6 and tumor necrosis factor-α (TNF-α) were detected by enzyme-linked immunosorbent assay; cell apoptosis in ischemic penumbra of cerebral cortex was detected by TUNEL; the expressions of adenosine monophosphate activated protein kinase (AMPK), endothelial nitric oxide synthase (eNOS) and nuclear factor κB (NF-κB) mRNA were measured by reverse transcription-polymerase chain reaction (RT-PCR); the protein expressions of p-AMPK, AMPK, p-eNOS, eNOS and NF-κB were detected by Western blot. Results Astaxanthin could significantly improve neurological function and cerebral infarction area in rats with cerebral infarction (P＜0.01), inhibit the expression of pro-inflammatory factors IL-1β, IL-6 and TNF-α, promote the expression of anti-inflammatory factor IL-10 (P＜0.05), reduce the cell apoptosis rate of cortical ischemic penumbra (P＜0.01), down-regulate the expressions of NF-κB mRNA and protein, and promote phosphorylation of AMPK and eNOS (P＜0.05), but there was no significant difference in the expressions of AMPK, eNOS mRNA and protein (P＞0.05). Conclusion Astaxanthin can significantly improve neurological function, cerebral infarction area, cell apoptotic rate of cortical ischemic penumbra and serum cytokines in rats with cerebral infarction, and its mechanism may be closely related to AMPK/eNOS/NF-κB signal pathway.