Objective-To evaluate efficacy and safety of IP administration of high-molecular-weight carboxymethylcellulose (HMW CMC) for the prevention of postoperative intra-abdominal adhesions in ponies. Animals-10 ponies. Procedure-A 1% solution of HMW CMC was instilled intra-abdominally prior to surgery in 5 ponies, whereas 5 control ponies did not receive HMW CMC. Postoperative adhesions were induced by use of a bowel-abrasion method comprising laparotomy, typhlotomy, and abrasion of jejunal serosa at multiple sites with placement of 3 sutures at each site. Day of surgery was day 0. After surgery, ponies were monitored, and hematologic, serum biochemical, and peritoneal fluid analyses were performed on days 1, 2, 3, 5, 7, and 10. On day 10, ponies were euthanatized. Intra-abdominal adhesions were recorded, and tissue samples were collected for histologic examination. Results-A significantly greater number of adhesions, number of multiple adhesions, and mean incidence of adhesions were identified in control ponies, compared with CMC-treated ponies. Mean peritoneal fluid WBC count on day 7 and serum fibrinogen concentrations on days 5 and 7 were significantly higher in control ponies, compared with CMC-treated ponies. Results of serum biochemical analyses did not differ significantly between the 2 groups. Conclusions and Clinical Relevance-Intra-abdominal use of 1% HMW CMC during surgery was effective for preventing postoperative adhesions in ponies. Use of HMW CMC did not have detrimental effects on wound healing, intra-abdominal defenses, or patient health. A 1% solution of HMW CMC may be used routinely during abdominal surgery of horses for prevention of postoperative adhesions.