The Morella salicifolia bark is used as a traditional medicine for the treatment of toothache, headache and stomachache in the eastern Ethiopia. The stem bark of the plant was sequentially extracted with: petroleum ether, chloroform and chloroform/methanol (1:1) using Soxhlet apparatus. Phytochemical screenings tests were conducted on of stem bark this plant extracts were performed on petroleum ether, chloroform and chloroform/methanol (1:1) crude extracts. The results showed presence of alkaloid, tannins, saponins, flavonoid, protein, and triterpenoids in the petroleum ether extract; alkaloid, tannin, flavonoid, protein, triterpenoid and absence of saponins chloroform extract; tannin, flavonoid, triterpenoid and absence of alkaloid, tannin, saponins and protein in the chloroform/methanol (1:1) extract. Volatile oil of the stem bark of plant was analyzed by GC-MS and it constitute 14 compounds among which the major compounds were hexadecanoic acid methyl ester (29.40%), (Z)-9‑octadecenoic acids and methyl ester (28.64%). The volatile oil and crude extracts of the stem bark were tested in vitro for their antimicrobial activity by disk diffusion method. The highest activity was exhibited by volatile oil, CHCl 3 /MeOH (1:1) and petroleum ether extract against Shigela flexneri , Escherichia coli and Streptococcus agalactiae with an inhibition diameter of 21.66, 17.66 and 18.00 mm, respectively. KEY WORDS : Antimicrobial activity, Disk diffusion, Morella salicifolia , GC-MS analysis Bull. Chem. Soc. Ethiop. 2019 , 33(2), 293-306. DOI: https://dx.doi.org/10.4314/bcse.v33i2.10