Adiponectin is synthesized by adipocytes and affects glucose and lipid metabolism by binding to its receptors, AdipoR1 and AdipoR2. Cysteamine, a naturally existing intermediate metabolite of sulfur amino acid, has been reported to modulate metabolism and growth in various species of animals; however, whether the action of cysteamine involves adiponectin and its receptors is unknown. The objective of the present study was therefore to investigate the effect of dietary cysteamine on the expression of AdipoR1/R2 in different tissues, in association with the alterations in endocrine and metabolic status. Rats were fed either of the diets supplemented with 0 or 700 mg/kg cysteamine feed additive (containing 30% of cysteamine hydrochloride) for 4 weeks, and the expression of adiponectin and its receptors in adipose tissue, AdipoR1 and AdipoR2 in liver, gastrocnemius, and soleus muscle was determined, in association with the growth performance and serum concentrations of hormones and metabolites. A temporal trend of increase in growth rate and the ratio of feed consumption relative to body weight gain was observed in the second week of cysteamine supplementation. Serum concentrations of insulin and TNF-alpha increased, while serum levels of triglycerides, FFA, and total cholesterol decreased significantly 4 weeks after cysteamine treatment. Leptin and GH remained unaffected. Cysteamine supplementation increased mRNA expression of AdipoR1 in adipose tissue, gastrocnemius, and soleus muscle as well as that of AdipoR2 in soleus muscle and adipose tissue. Nevertheless, hepatic expression of AdipoR1 and AdipoR2 was not influenced. Despite a numeric increase, no significant alteration in adiponectin mRNA expression in adipose tissue was observed. In conclusion, dietary supplementation of cysteamine modulates the endocrine and metabolic status of rats, which may involve the tissue-specific responses of adiponectin receptors at the level of mRNA transcription.