Introduction: The purpose of this study is to investigate theeffects of tetracycline (TC), clarithromycin (CM) and bleomycin(BLM) on the cyst diameter and ovarian tissues in the treatmentof simple ovarian cysts.Methods: We employed Wistar albino female rats (n=38) tocreate ovarian cysts, and did not intervene in any form in thecontrol group (GC) (n=6). In total, 32 female rats underwentunilateral salpingectomy for the creation of cysts. Macroscopiccysts were manifested in 25 (78%) rats who underwentsalpingectomy. We divided the rats (n=25) with cysts intofour groups. Salpingectomy with saline was performed in G1,salpingectomy with tetracycline (TC) was performed in G2, andsalpingectomy with Clarithromycin (CM) was performed in G3.Additionally, salpingectomy with BLM was exploited in G4.Results: There was a significant decrease in the diameter ofthe cyst in G2 as compared to G1, but there was no significantdifference among the other groups. There was no significantchange in total ovarian reserve in the groups (p=0.066).There was a statistically significant increase in fibrosis in G1and G3 groups as compared to GC (p<0.0001). As comparedto G1, fibrosis was significantly decreased in G2 (p=0.003) andG4 (p=0.0001). TUNEL positivity was similar in GC and G1;however, there was a significant increase of TUNEL positivityin G2, G3 and G4 as compared to the control group (p<0.0001).In addition, there was a significant increase of adhesion in G2(p=0.030) and G3 (p=0.010) as compared to G1.Conclusion: TC is a more effective agent than CM and BLM inthe sclerotherapy treatment of ovarian cysts. These three agentshave no negative effect on the total ovarian reserves. There isan increasing need for further clinical studies regarding the use of sclerotherapy agents, primarily concerning the TC, inthe treatment of simple ovarian cysts.