AbstractLaminitis associated with equine metabolic syndrome causes significant economic losses in the equine industry. Diets high in non‐structural carbohydrates (NSC) have been linked to insulin resistance and laminitis in horses. Nutrigenomic studies analyzing the interaction of diets high in NSCs and gene expression regulating endogenous microRNAs (miRNA) are rare. This study's objectives were to determine whether miRNAs from dietary corn can be detected in equine serum and muscle and its impacts on endogenous miRNA. Twelve mares were blocked by age, body condition score, and weight and assigned to a control (mixed legume grass hay diet) and a mixed legume hay diet supplemented with corn. Muscle biopsies and serum were collected on Days 0 and 28. Transcript abundances were analyzed using qRT‐PCR for three plant‐specific and 277 endogenous equine miRNAs. Plant miRNAs were found in serum and skeletal muscle samples with a treatment effect (p< .05) with corn‐specific miRNA being higher than control in serum after feeding. Endogenous miRNAs showed 12 different (p< .05) miRNAs in equine serum after corn supplementation, six (eca‐mir16, ‐4863p, ‐4865p, ‐126‐3p, ‐296, and ‐192) previously linked to obesity or metabolic disease. The results of our study indicate that dietary plant miRNAs can appear in circulation and tissues and may regulate endogenous genes.