The enthalpies of dilution of matrine (MAT) in pure water and aqueous sodium chloride solutions were determined by isothermal titration microcalorimetry at 298.15 K, and the corresponding homogeneous enthalpic interaction coefficients were calculated according to the modified McMillan–Mayer model. The values of enthalpic pair-wise interaction coefficients, h2, are all positive and become more positive with increasing concentration of sodium chloride.