The kinetics of the reaction of 5-nitro isatin with morpholine in presence of wateracetonitrile and water-methanol solvents, was followed spectrophotometrically in the ranges of solvent composition (10–90%v/v) and temperature (25–45°C) using morpholine as a nucleophile. The reaction was second order rate. The rate of reaction strongly decreased with increasing organic solvent content and strongly increased with increasing water content in both water-acetonitrile and water-methanol solvents. The rate of the reaction in acetonitrile- water mixed solvent is found to be larger than that in methanol-water solvent . The NO2 substituent on the C5 increases the reaction rate. The thermodynamic activation parameters were calculated and discussed in terms of solvation. Both linearity and non-linearity was observed between log (rate constant) and reciprocal dielectric constant for both solvents used, suggesting that the reaction of 5-nitroisatin with morpholine depend on specific as well as nonspecific solvation of the medium. The reactivity was analyzed in the light of various simple, dual and multiple regression equations using Kamlet–Taft solvatochromic parameters which were applied successfully to the mixed aqueous–acetonitrile aqueous-methanol mixtures. Finally, a mechanism for the reaction is proposed.