Pharmacological and barrier-based approaches have been exploited for the treatment of post-surgical adhesion. In this study, anti-coagulating hydroxyethyl starch (HES) blended with hyaluronic acid (HA) was assessed as a novel post-surgical adhesion barrier in Sprague-Dawley (SD) rats to take advantage of both approaches. The HES/HA blend solution effectively reduced the adhesion area to 6.5% of the control, which might be due to the inhibited blood coagulation by HES as well as highly effective barrier properties of hygroscopic high molecular weight HA. Histological analysis showed that the HES/HA blend solutions effectively protected the smooth muscle cells and skeletal muscle cells from muscle degeneration by adhesion in the abdominal walls of SD rats.