Abstract: The present study was designed to differentiate between the effect of propofol and ketamine HCL on both clinical and blood parameters in detomidine pre-medicated Egyptian donkeys. Six apparent healthy donkeys were divided into two equal groups. All animals were pre-medicated by 0.2 mg/kg detomidine intravenously, then the first Group (G1) was injected by the propofol (2 mg/kg intravenously) while the second Group (G2) was injected by ketamine HCL (2.2 mg/kg intravenously). The onset, duration and recovery periods were calculated for each group. Heart rate, respiratory rates and body temperatures were recorded. Blood samples were collected at 0, 15, 30, 60 min and 6 h after the anesthetic drug injected for record any changes were done in blood parameters. Results showed that the onset, duration and total recovery periods of anesthesia were 6.35±3.08 and 4.52±1.23, 29.44±2.51 and 42±1.00 and 62±2.48 and 85.33±3.11 min in G1 and G2, respectively. In G1, marked decrease in RBCs, PCV and Hb values from the zero time and presence of shallow respiration. However, no detectable changes in blood parameters were detected in G2. In conclusion, these findings indicate that ketamine in detomidine pre-medicated donkeys produced rapid induction, long duration, smooth induction, recovery and sufficient anesthesia without any significant changes in all parameters. So, using of ketamine to produce sufficient anesthesia is better in detomidine pre-medicated Egyptian donkeys in compare with the propofol.