Introduction: Beta (β) endorphins have been detected in the hypothalamus and pituitary, and in a small amount in other organs. The aim of our study was to establish the possible influence of psychotropic drugs on serum and brain β-endorphins in rats as experimental model. Material and methods: The study was performed on albino Wistar rats (200-250 g body weight), using the antidepressant trazodone. RIA technique was employed for quantification of serum and brain β-endorphins. Results: Serum β-endorphins measured on day 1 of trazodone application were significantly higher (72.31 ± 1.86 pg/mL; x± SEM) compared to baseline values (45.83 ± 3.77 pg/mL; P = 0.001). However, trazodone produced significantly lower β-endorphin concentrations on day 9 of treatment (33.4 ±1.91 pg/mL) compared to the values measured on day 1 of trazodone administration (P = 0.001). Endorphin concentrations recorded on day 28 (38.62 ± 1.42 pg/mL) were higher compared to those measured on day 9 (P = 0.439). Data on brain β-endorphin concentration showed a significant decrease on day 1 of trazodone administration (431.03 ± 11.57 pg/g) compared to data obtained from control rat brains (873.5 ± 18.32 pg/g; P = 0.001). Statistical significance was also recorded by comparison of the lower data obtained on day 9 of treatment (433.65 ± 14.67 pg/g) and those observed in the control group (P = 0.001). In trazodone treated rats, brain β-endorphins were significantly higher on day 28 (929 ± 18.13 pg/g) compared with the levels measured on day 1 and day 9 of treatment (P = 0.001 both), showing slightly higher values than in control rats, yet without statistical significance (P = 0.137). Conclusion: Chronic trazodone treatment causes an increase in the brain β-endorphin synthesis, while acute drug administration results only in a rapid release of β-endorphins into the circulation.