Background/Objective: Ghrelin is a peptide hormone known to play a role in glucose homeostasis; therefore, functional variants of the human ghrelin gene could contribute to the genetic susceptibility to diabetes or may modulate some aspects of the glucose intolerance phenotype. The study aimed at investigating the differences in the frequencies of Arg51Gln polymorphisms among Egyptian patients with type II diabetes and healthy control subjects and at verifying whether this polymorphism could influence the diabetes phenotype. Methods: One-hundred-four Egyptian type II diabetic patients attending the Medical Research Institute were enrolled into the study. Clinical data concerning medical and family history were collected by a clinical interview.  Another group of 100 non-diabetic apparently healthy subjects were included to compare the Arg51Gln genotypes frequencies. The ghrelin Arg51Gln polymorphism was studied by PCR restriction fragment lengthpolymorphism method in the diabetic and control subjects. The metabolic profile of the diabetic patients was also analyzed. A X² test was adopted to compare the ghrelin Arg51Gln genotype and allele frequencies among the two groups. Moreover, in order to test whether the differences in phenotypic variables between the patient groups were influenced by ghrelin genotype, ANOVA test was performed. Results: The frequency of the 51gln heterozygotes and homozygotes were significantly higher in the patients' group than in the control sample (X² =8.962, p= 0.0113). The 51gln allele frequency was higher in the patients than in the control group (q=0.27 and q=0.14, respectively); a difference that was found statistically significant (X² =5.185, p= 0.022).  The fasting blood sugar and triglycerides levels were higher in patients carrying the ghrelin 51Gln allele than in those with the wild allele (statistically significant, p=0.014 and p=0.004, respectively). No statistically significant difference was observed between the total cholesterol, HDL and LDL cholesterol concentrations among these two groups. Conclusions: There is a significant positive association between ghrelin 51Gln polymorphism and type II diabetes in the Egyptian population. Further studies are warranted to elucidate the role of ghrelin in the development of thisdisease.