Background: Various extracts from Citrullus colocynthis seeds were recently examined for their possible favorable effects on glucose homeostasis, other metabolic variables, and pancreatic islet size in streptozotocin-induced diabetic rats. Objective: Considering the effectiveness of insulin upon target cells as another process susceptible to be influenced by plant extracts, the present study is used to compare the effects of either crude or defatted aqueous extracts from C. colocynthis seeds upon Na+ transport in A6 kidney cells. Method: The intensity of electrical currents, taken as the potential difference divided by the epithelial resistance was measured in monolayers of A6 kidney cells exposed at the basolateral side to either crude untreated aqueous (EI) or defatted aqueous (EII) extracts, as well as their fractions EI1 and EII1 containing components with high molecular weight (> 5 kDa), and EI2 and EII2 containing components with low molecular weight (< 5 kDa). The effect of insulin was to assess the functional integrity of the A6 monolayer. Results: All extracts caused a rapid and sustained increase in current intensity. The defatted aqueous extract (EII) was more efficient than the non-defatted aqueous extract (EI) in terms of increasing the intensity of current in the A6 monolayer. The components of the defatted aqueous extract responsible for such a greater efficiency were located in the fraction containing components with low molecular weight and acted in a time-related progressive fashion upon Na+ transport. Conclusion: These data suggest that colocynth seed extracts mainly containing components with low molecular weight increased the current intensity in A6 cells, thus suggesting that colocynth may affect Na+ transport in kidney cells.