Ketoprofen is used to treat painful conditions such as arthritis, sprains and strains, gout, period (menstrual) pain, and pain after surgical operations. It eases pain and reduces inflammation. After oral administration it can have side effects especially on digestive system. That's why it is recommended with caution. In recent years we could note an orientation towards topical administration of NSAIDSs and hydrogels occupy one of the first places through the forms that were developed for topical use. Five different experimental formulations coded G1 to G5 containing 1% Carbomer 940 as gel forming agent were prepared in order to evaluate influence of both composition and preparation methodology on ketoprofen (KTP) diffusion kinetics. Release of KTP from the various gel formulations was studied using a modified Franz diffusion cell fitted with a standard cellophane membrane. The release profiles for all the experimental formulations as well for one commercial product (Fastum (R) gel) were compared in terms of diffusion coefficients (D). The hydrogel formulated with isopropyl alcohol, presented the slowest release of KTP, whereas the gels using ethanol and propylene glycol respectively were similar, yielding about 60% of the incorporated substance after 5 hours. Moreover, for the preparation of the KTP gels we recommend prior dissolution of the drug in the amount of the alcohol from the formulation. The release profile of the commercial formulation is intermediate between those of the experimental hydrogels. To establish the drug release mechanism from the tested hydrogels, several kinetic models were investigated: zero order, first order, Higuchi and Korsmeyer-Peppas models. For the tested hydrogel, the release mechanism is as follows: (i) Fickian diffusional model for the commercial product; (ii) zero order for the hydrogels GI-G4 (the release mechanism is represented by a time-independent case-II, relaxational transport); (iii) a complex mechanism for hydrogel G5, super case-II transport, where the diffusion is associated with hydrogel network swelling and destructuration, most probably due to its sensitivity by mechanical action during preparation. The results obtained confirmed that the KTP in vitro release kinetics, is influenced both by the type of alcohol from the gel basis and the preparation methodology, these variables being able to modify the bioactive compound release mechanism.