Description: To determine the effect of short-term hyperinsulinemia on the localization and expression of endothelin receptor (ETR)-A and ETR-B in lamellar tissue of the forelimbs of horses. Samples-Distal portion of 15 cadaveric forelimbs from healthy adult horses (1 limb/horse) obtained immediately after slaughter at an abattoir. Procedures-Each forelimb was assigned to 1 of 3 treatment groups (perfused with autologous blood for 10 hours [control perfusion; n = 5], perfused with an insulin [142 с 81 ?U/ mL] perfusate for 10 hours [insulinemic perfusion; 5], or not perfused [unperfused control; 51). Immunohistochemical evaluation of lamellar tissue was performed to assess localization of ETR-A and ETR-B. Expression of ETR-A and ETR-B was measured semiquantitatively on a scale of 0 to 3 (0 = none, 1 = mild, 2 = moderate, and 3 = high-intensity staining) and quantitatively by means of gray value analysis with imaging software. Results-In all specimens, ETR-A and ETR-B were localized in endothelium, smooth muscle cells, axons, and keratinocytes. Quantitative expression of ETR-A in the midportion of the primary epidermal lamellae for the insulinemic perfusion group (149 с 16) was lower than that for the control perfusion group (158 с 15). Expression of ETR-B in the primary epidermal lamellae tips for the insulinemic perfusion group (140 с 29) was higher than that for the control perfusion group (114 с 8). Conclusions and Clinical Relevance-Hyperinsulinemia caused significant changes in endothelin receptor expression, which suggested that ETR antagonists might be beneficial for treatment of laminitis in horses