To study the effect of prostglandin E_² and evening primrose oil on orthodontic tooth movement in rats, one hundred and sixty rats were divided into four groups of 40 rats each. One group, injected with saline on the palate subperiosteally, served as a control group. A second and third group were injected subperiosteally on the palate with PGE_² 10µg and evening primrose oil 10mg respectively. The fourth group was given indomethacin 20µg/ml orally by water bottle. The maxillary first molar was moved mesially from the incisors using a 50gm force rubber band. In each group at the 1, 2, 3, 5, and 7th day, 4 rats were examined by light microscope, and 4 by electron microscope. The obtained results were as follows: 1. Osteoclastic activity was maximum at the 3rd day in the PGE_² group on the interradicular alveolar bone of the first molar, followed by the evening primrose oil group, control group, and indomethacin group. 2. Root resorption and vacuolar changes were maximum in the PGE_² group. 3. At the 3rd day of the PGE_² group, the osteoclasts showed well developed ruffled borders and clear zones. At the same day, the evening primrose oil group also showed well developed ruffled borders and clear zones, but less than the PGE_² group. 4. At the 3rd and 5th day of the PGE_² group, fibroblasts showed phagocytized fragmented collagen fibers in the cytoplasm. At the 7th day of the PGE_² group, fibroblasts showed collagen fibers forming at the cell membrane surface.