Objective To investigate the protective effect of the combination of glutamine (Gln) and ar-ginine (Arg) on intestinal barrier function in rats receiving fluorouracil (5-FU) chemotherapy.Methods Totally 40 male SD rats receiving 5-FU chemotherapy were equally randomized into four groups:enteral nutrition group,Gln group (enteral nutrition+Gln),Arg group (enteral nutrition+Arg),and Arg+Gln group (enteral nutri-tion+Arg+Gln).Observe the changes post chemotherapy such as the changes of body weight and urine lactulose/mannitol ratio before and after chemotherapy were recorded.On the 8 th post-therapy day,the blood endotoxin level in portal vein was measured,and lymph nodes and blood in portal vein were taken for bacterial culture;colon and jejunum specimens were also taken to measure the height of jejunum villus and the thickness of colon and jejunum.Results Body weights of Gln group,Arg group,and Arg+Gln group significantly increased after chemotherapy (P<0.05).The change of body weight was significantly lower in Arg+Gln group than in Gln group (P=0.002),while no such difference was found when compared with that in Arg group (P>0.05).Lactulose/manni-tol ratio in each group significantly increased after chemotherapy (P<0.05),and the change of lactulose/mannitol ratio was significantly higher in the enteral nutrition group than those in other groups (P=0.000);however,no such difference was found among other groups (P>0.05).The blood endotoxin level in portal vein was signifi-cantly higher in enteral nutrition group than in other groups (P=0.000);the endotoxin level was significantly lower in Gln group than in Arg group (P=O.035) and Arg+Gln group (P=0.000);however,no such differ-ence was found between Arg group and Arg+Gln group (P=0.109).The height of jejunum villus and the thick-ness of jejunum were significantly lower in enteral nutrition group than those in the other groups (P=O.000);the thickness of colon was significantly lower in enteral nutrition group than those in Arg group and Arg+Gln group (P=0.000);however,no such difference was found when compared with Gln group (P=0.058).The thickness of colon (P=0.040) and jejunum (P=0.010) was significantly higher in Gln group than that in Arg group;but there was no significant difference in term of the height of jejunum villus (P=0.286).Compared with Arg+Gln group,the thickness of jejunum in Gln group was significantly higher,but there was no significant difference in terms of the height of jejunum villus (P=0.286) or the thickness of jejunum (P=0.190).The thickness of co-lon was significantly lower in Arg group than in Arg+Gln group (P=0.010),while no such significant difference was found in terms of the height of jejunum villus (P=0.803) or the thickness of colon (P=0.059) when com-pared with Arg+Gln group.The bacterial culture results were not significantly different among all groups.Conclu-sions The combination of Arg and Gln has protective effects on intestinal barrier in rats receiving 5-FU chemother-apy.The protective effect of Gln is superior to that of Arg.No synergistic effect exists between Arg and Gln.