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Objective To observe the dynamic changes in plasma levels of neuropeptide Y (NPY) in patients with acute cerebral infarction (ACI) and the serum nitric oxide synthase (NOS) in order to find out the relationship between each other as well as their clinical significance. Method A prospective and control study was done in 30 patients with ACI including 21 male and 9 female with average age of (58.07 ± 12. 1S) years admitted from May 2008 to March 2009. These patients hit the diagnostic criteria for cerebral infarction (CI) set by the Chinese Society for Neruoscience and the Chinese Association of Neurosurgery in 1996 for their first attack of CI was treated within 48 hours. Patients with acute myocardial infarction, peripheral vascular disease, infection, tumor,or severe organic functional impairment, etc within six months were excluded. Another 27 healthy subjects asking for routine physical examination including 15 male and 12 female with average age of (55.00± 11.03) years were included as control group at the same period. The two groups were comparable. The blood samples of fasted subjects of control group and CI patients 48 hours after and within 10 days after attack were taken to examine the level of NPY by using radioimmunoassay and the level of serum NOS by using chemical colorimetry. The size of responsible focus of CI was calculated, and the degree of neurological deficits were estimated with Stroke Scales set by the American National Institutes Of Health (NIHSS). The chi-square test was used for constituent ratios within samples, while t -test was applied to analysis of differences between two groups, and linear was used for bivariate simple correlation analysis. Results (1) There was no significant difference in NPY between two groups. (2) The level of constructional NOS (cNOS) within 48 hours after attack in CI group was significantly lower than that in control group, and it was significantly and negatively correlated with the size of infarction and the NIHSS scores at the same period, whereas it significantly and positively correlated with difference in NIHSS scores, while it increased more significantly 10 days after attack than it did within 48 hours after attack. (3) The level of inducible NOS (iNOS) within 48 hours after attack in CI group was significantly higher than that in control group, and it was significantly and positively correlated with the size of infarctionand NIHSS scores at the same period, and it significantly and negatively crrelated with the difference in NIHSS scores, while it decreased more significantly 10 days after attack than it did within 48 hours after attack. (4) The level of NPY was not correlated with both cNOS and iNOS in CI group. The difference in levels of NPY was negatively and significantly correlated with the difference in levels of cNOS. Conclusions There was no significant change in plasma NPY level in ACI patients, and it was not correlated significantly with the disease itself. The serum cNOS was negatively correlated with the disease itself significantly within 48 hours after attack. The iNOS level was positively correlated with the disease itself significantly, and it reflected the severity of CI within 48 hours after attack. The changes of NPY level in plasma were significantly and negatively correlated with the changes of cNOS level in serum within 48 hours and 10 days after attack.