Viscosity-enhancing agents such as carboxymethylcellulose (CMC) can alter absorption of solutes and fluid exchange in the small intestine. We investigated whether the standard World Health Organization oral rehydration solution (WHO-ORS) with the addition of CMC would improve net water and sodium absorption in rats using an in vivo intestinal perfusion technique. Four WHO-ORS, containing either 0, 2.5, 5.0, or 10.0 g/L of CMC, were perfused in rats with a well-tested model of cathartic-induced chronic osmotic diarrhea (D) and in normal controls (C). In D rats, the ORSs with CMC improved sodium absorption at the three concentrations used (p < 0.01). The same effect was shown in C rats. Net water absorption was also enhanced in D rats given ORSs with CMC, although the changes in C animals were less marked. The improvement in sodium and water absorption in both C and D rats positively correlated with the log of relative ORS viscosity. Ultrastructural examination of tissues perfused with 10 g/L of CMC showed an extended brush border glycocalyx. This study indicates that CMC added to WHO-ORS in the perfused rat jejunum improves the effectiveness of the solution by increasing sodium and water absorption.