The ob/ob leptin-deficient mouse is hyperglycemic and obese. We used 14-week old ob/ob and lean mice. The goal of this study was to characterize jejunal function in this clinically relevant mouse model. We measured transepithelial short circuit current (Isc), across freshly isolated segments of jejunum. Basal Isc was significantly decreased 2-fold, in the ob/ob mice (50.5±9.5 µA/cm2, n=5) compared to lean mice (95.2±20.3 µA/cm2, n=4, P<0.05). The Isc in response to forskolin (10 µM, bilateral), bumetanide (100 µM, basolateral), and acetazolamide (100 µM, bilateral) was similar for ob/ob and lean mice. Jejunum morphology indicates that crypt depth was similar for both groups, and thus structural changes do not contribute towards the reduced Isc of the ob/ob mice. Villi length was significantly increased (by ~100 µm) in the ob/ob mice, suggesting a greater surface area for absorptive function. Expression of the transporter protein, Glut5 (normalized to GAPDH), was significantly increased in ob/ob mice 0.74±0.06 (n=l4, P<0.05), compared to leans (0.37±0.06, n=l l), whereas, expression of the Glut2 transporter was similar for both groups. These data suggest that basal jejunal Isc in ob/ob mice is ~1/2 that of lean mice, and may reflect slower transit times in the gastrointestinal tract in the ob/ob mice, which may contribute towards increased nutrient absorption (specifically increased fructose uptake via Glut5), increased weight gain, and the associated diabetic phenotype. The contribution of key jejunal epithelial transporters is under investigation.