Sepsis is the most common cause of acute kidney injury in ICU patients, with increasing mortalities. Treatment septic AKI is unsatisfactory; therefore, more effective therapies must be investigated. MSCs-MVs have the same effectiveness in tissue repair as their original cells. Granulocyte colony- stimulating factor (G-CSF) is considered a simple and convenient tool in regenerative medicine. This study aimed to compare the probable therapeutic effect of MSCs-MVs versus G-CSF on septic AKI in rats. Forty-eight adult male rats were divided into four groups; I control group (IA-ID), II induced- sepsis group, III G-CSF, and IV MSC-MVs groups. Sepsis was induced in groups II, III, IV through a single IV injection of 10 mg/ kg of E.Coli-LPS dissolved in 1 ml saline. Four hours later, group IV received a single IV injection of MSCs-MVs, while group III received a SC injection of Neupogen for 5 days. All animals were sacrificed 7 days from the start. Serum and tissue samples of each group were used for biochemical study. Sections from all groups were subjected to light and electron microscopic examination. A fluorescent microscope examination for subgroup ID and group IV was done. Morphometric and statistical analyses were performed. Group II showed features of acute tubular injury. Group III showed some improvement (biochemically, LM & EM level) however, group IV showed more improvement. MVs injection caused a marked improvement in septic AKI; G-CSF can also meliorate the degenerative effect of sepsis on renal cortex, but to a lesser extent than MSCs-MVs.