Aims <p>Diabetes induces skeletal muscle atrophy and capillary regression, especially in oxidative muscles, such as the soleus (SOL). Capillary regression impairs oxygen and substrates delivery, and contributes to metabolic dysfunction and vascular complications. Although protective effects of antioxidants have been demonstrated in disuse models, their role in diabetes-induced capillary regression remains unclear. We examined whether dietary astaxanthin supplementation attenuates capillary regression in the SOL muscles of rats with streptozotocin-induced diabetes.</p> Methods <p>Twenty-four male Wistar rats (6 weeks old) were randomly divided into three groups: control (CON), streptozotocin-induced diabetes (STZ), and STZ with astaxanthin supplementation (STZ + AST). Diabetes was induced by a single tail vein injection of streptozotocin (STZ; 50&#xa0;mg/kg). Astaxanthin (100&#xa0;mg/kg/day) was orally administered to the STZ + AST group for 6 weeks. The SOL muscles were analyzed for the capillary-to-fiber (C/F) ratio, oxidative stress (dihydroethidium [DHE] staining), and expression of angiogenesis- and AGEs-related proteins by western blotting.</p> Results <p>Rats in the STZ group exhibited decreased muscle C/F ratio, increased DHE fluorescence, and elevated FOXO1 and TSP-1. Astaxanthin supplementation significantly improved the C/F ratio and reduced excessively generated ROS and anti-angiogenic protein expression. In addition, the VEGF-A/TSP-1 ratio improved in the STZ + AST group rats. Although the RAGE levels remained elevated, a downward trend was observed following astaxanthin treatment.</p> Discussion <p>Astaxanthin supplementation attenuated diabetes-induced capillary regression in the SOL muscles by suppressing oxidative stress and modulating angiogenic signaling. These findings suggest a therapeutic potential for protecting the skeletal muscle microvasculature under diabetic conditions.</p>