Background: Diabetic retinopathy (DR) is a common microvascular complication of diabetes and a leading cause of blindness. Astaxanthin (AST) is a naturally occurring carotenoid with many biological protective activities. The purpose of the present study was to investigate the protective effects of AST on DR in a rat model of type 1 diabetes mellitus (DM) and to examine the mechanisms involved. Methods: An intraperitoneal injection of 1% streptozotocin was used to prepare the rat model of diabetes. Rats were randomly assigned to one of three groups: untreated control, diabetes + olive oil (DM), or DM+AST (n = 8 per group). The AST group received 20 mg/kg/day AST dissolved in olive oil by gavage. The DM group received an equal volume of olive oil. During the study, blood glucose levels and body weights were measured every two weeks. After six months, retinas were excised to prepare the retinal capillary network. Endothelial cell to pericyte ratio (E/P) and the numbers of acellular capillary strands were compared among different experimental groups. Formation of advanced glycation end products (AGEs) and expression of interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha), and caspase-3 in retinal tissues were assessed by immunohistochemistry and RT-PCR. Results: AST slightly increased body weight but had no significant effects on blood glucose levels. E/P and numbers of acellular strands in the DM+AST group were lower than those in the DM group. Expression of AGE, IL-6, TNF-alpha, and caspase-3 in retinal tissues decreased compared with those of the DM group. All differences between the groups were statistically significant (P < 0.05). Conclusion: AST can protect pericytes from apoptosis and delay development and progression of DR in streptozotocin-induced diabetic rats. Additionally, it can reduce generation of AGEs, release of inflammatory cytokines (IL-6, TNF-alpha), and cleavage of caspase-3, which may mediate pericyte apoptosis.