Phosphodiesterase activity was tested on homogenized eyes of pre-diabetic rats kept in normoxic, hypoxic and hyperoxic conditions, with the aim of correlating any difference in PDE activity with variations in atmospheric oxygen contents. The activity of the cAMP phosphodiesterase (cAMP-PDE) was tested. Phosphodiesterases seem to be particularly susceptible to variations in oxygen tension, suggesting an important role of cyclic nucleotides in adaptive processes of the cell. cAMP-PDE activity increases slightly in normoxic, hypoxic and hyperoxic conditions in pre-diabetic rats. The second messenger, cAMP, plays important roles in mediating the biological effects of a wide variety of first messengers. The intracellular levels of cyclic nucleotides depend upon rates of synthesis and degradation, of cyclases and phosphodiesterase (PDEs), respectively. Therefore, PDEs seem to play an important role in a wide variety of physiological processes.