A two-molecule chitinolytic enzyme system (endo- and exo-chitinase) hydrolyzes and degrades the chitin polymers. Therefore, it is imperative to discover novel compounds for inhibiting chitinolytic enzymes to prevent insect growth. This research examined the effect of pentoxifylline (a dimethylxanthine chitinase inhibitor) on inhibition of endo- and exo-chitinolytic enzyme activities in eastern subterranean termite, Reticulitermes flavipes (Kollar). Enzyme activities were compared with amounts of treated diet consumed by termites and percent mortality observed over time. Pentoxifylline affected in vitro endo-chitinase activity in a concentration-dependent manner, while having minimal to no effect on in vitro exo-chitinase enzyme activity. However, pentoxifylline treatment affected in vivo endo- and exo-chitinase enzyme activity and caused measurable termite mortality. Moreover, pentoxifylline concentrations did not deter the amount of diet consumed by termites, thereby suggesting that it is palatable. The results of this study support further exploration into termiticidal activity and potential use of pentoxifylline for termite control.