Solvent effects on 3-keto-1H-pyrido[3,2,1-kl]phenothiazine (PTZ-5) fluorescence in aprotic and protic solvents were investigated using the time-dependent density functional theory method. Enhancement of PTZ-5 fluorescence in the polar aprotic solvent is caused by the decoupling of the two proximity low-lying excited singlet states. In polar protic solvents, aside from the solvent polarity effects, hydrogen-bonding effects are significant to the enhancement of fluorescence. Hydrogen bonds confine C-H out-of-plane bending and severely decouple the two low-lying excited singlet states, greatly decreasing nonradiative decay. The excited state intermolecular proton transfer model is considered a quenching reaction for excited PTZ-5; however, it is uncompetitive in excited-state dynamics.