Optical waveguide spectroscopy (OWS) was employed to monitor the swelling behavior of pulsed plasma polymerized maleic anhydride (PPPMA) films in humid air and in aqueous solutions by measuring the film thicknesses and refractive indices. With the relative humidity of air increasing, both the thickness and the refractive index of the PPPMA films increased, indicating water penetration into and uptake by the films. The swelling of the hydrated PPPMA films in humid air is reversible. In aqueous media, the thickness and the refractive index of the washed PPPMA film increased with an increase of pH and ionic strength, respectively. On the basis of the present data, a hypothesis concerning the structure of the PPPMA film is proposed. Our model suggests that the unique structure of the PPPMA films originates from the cyclic structure of maleic anhydride and depends on parameters of the plasma deposition process, and the interaction between H2O and the carboxylic groups.