Selective intestinal decontamination withnorfloxacin is useful in preventing spontaneousbacterial peritonitis in cirrhotic patients and also incirrhotic rats. The emergence of norfloxacin-resistantinfections in these patients warrants a search foralternative therapies. The aim of this study was toevaluate the effect of long-termtrimethoprimsulfamethoxazole administration on carbontetrachloride (CCl₄)-induced cirrhosis inrats with specific attention to intestinal flora,bacterial translocation, spontaneous bacterialperitonitis (SBP), and survival. Male Sprague-Dawleyrats received CCl₄ administered weekly bygavage. After eight weeks of CCl₄administration rats were randomly allocated into twogroups. Group I received daily overnighttrimethoprim-sulfamethoxazole diluted in phenobarbital water during follow-up and groupII did not. The rats were killed when gravely ill, anda laparotomy was performed to culture samples of cecalstool, mesenteric lymph nodes, and portal and inferior vena caval blood. There was a trendtoward a reduction in the incidence of bacterialtranslocation (8/17 vs 11/14, respectively) and SBP(5/17 vs 7/14, respectively) in treated rats that werekilled just before death compared to untreated rats.A decrease in the incidence of bacterial translocationcaused by gramnegative bacilli was observed in group I(17.6% vs 78.6% , P < 0.01).="" the="" development="" of="" ascites="" was="" delayed="" in="" group="" i="" (p="">< 0.05)and="" survival="" was="" prolonged="" in="" group="" i="" (p="">< 0.05),despite="" a="" higher="">₄ dose in this group (P< 0.05).="" in="" conclusion,="" long-term="" prophylactic="" trimethoprim-sulfamethoxazole="" administration="">₄-induced cirrhosis in rats delayed thedevelopment of ascites, prolonged survival, and reducedthe incidence of gramnegative bacterial translocation but not of SBP, without increasinggram-positive episodes. These data suggest thattrimethoprim-sulfamethoxazole might be a goodalternative to norfloxacin for preventing gram-negativebacterial translocation.