The aim of this study investigate the effects of long term administration ofDexamethasone (DEX.) 17 β-estradiol (EST.) on body weight, concentration of somehormones ( Leptin, thyroid and reproductive hormone) in addition to determination oflipid profile of female rabbits blood serum.Thirty local rabbits were subdivided randomly and equally into three groups. Thefirst group was used as a control which injected with normal saline . The second groupwas injected daily (0.5mg /kg B.W) DEX . Intramuscularly. The third group was injectedsubcutaneously daily with 0.3 mg /kg B.W s/c 17 β-estradiol. All groups in this studywere treated for 60 days , and blood collected every 15 days. Serum was tested for leptin,LH, FSH, T3, T4 hormones total Cholesterol(TC), HDL(height density lipo-protein),LDL (low density lipo- protein),TG (triglycerides), Body weight was taken every 15 daysfrom the first day .The result showed significant (P≤0.05) decreased in body weight afteradministration of both dexamethasone (DEX.) and Estrogen (EST.), significant increasedin leptin concentration with dexamethasone (DEX.) Treatment while significantdecreased with Estrogen (EST.) treatment, in the other hand LH and FSH concentrationshowed significant decreased in both treatment dexamethasone (DEX.) and Estrogen(EST.) thyroid hormone show significant decreased with dexamethasone (DEX.)Treatment and significant increased T3 & T4 hormone with Estrogen (EST.) treatment ascompare with control while the increase in the T4 it was occurred only in the periods (45and 60)days within treatment groups , lipid profile (TC,TG,LDL, HDL,VLDL) showsignificant increased with DEX. treatment while Significant decreased with EST.treatment