Objective To explore the relationship between platelet to lymphocyte ratio （PLR）， lipoprotein-associated phospholipase A2 （Lp-PLA2）， homocysteine （HCY） and the diagnosis and short-term prognosis of ischemic stroke. Methods A total of 200 cases of ischemic stroke patients （case group） admitted in the Department of Neurology of the Affiliated Hospital of Xuzhou Medical University from October 2018 to October 2019 were recruited as the case group. The 120 health people taking physical examination at the same time were enrolled as the control group. All the patients were test for PLR， Lp-PLA2 and HCY levels. The patients in the case group were divided into mild， moderate and severe neurological deficit groups according to NIHSS score at admission. After 3 weeks of treatment，the patients in the case group were divided into good prognosis group and poor prognosis group according to modified Rankin Scale （mRS） score. The levels of serum PLR， Lp-PLA2， HCY were compared among mild to moderate severe neurological deficits in the case group and between good prognosis group and poor prognosis group respectively. The ROC curve was used to analyze the diagnostic efficacy and evaluated the prognostic value. Results Compared with the control group， the levels of PLR， Lp-PLA2 and HCY were significantly higher in the case group， with statistical significance ［（168.73±62.12） vs （116.87±31.87）， （245.64±81.30） μg/L vs（165.17±38.13）μg/L， （18.45±6.81） μmol/L vs （11.14±3.04） μmol/L； t=9.843，11.377，13.161； （P＜ 0.05）］.The results of binary logistic regression analysis showed that PLR， Lp-PLA2 and HCY were independent risk factors of ischemic stroke （OR=1.017，1.005，1.072； 95%CI：1.009-1.026，1.000-1.010，1.009-1.139；P＜ 0.01）. The levels of PLR， Lp-PLA2 and HCY of mild， moderate and severe neurological deficit groups were significantly different （P ＜ 0.01）. The follow-up results showed that the levels of PLR， Lp-PLA2 and HCY of the poor prognosis group were significantly higher than those of the good prognosis group 3weeks after discharge ［（204.75±65.08） vs （140.43±41.97）， （282.99±77.49）μg/L vs （216.29±71.89） μg/L， （21.76±7.02） μmol/L vs （15.86±5.40） μmol/L］， and the differences were statistically significant （t=8.048，6.293，6.716； P＜ 0.05）. The area under the curve of serum PLR， Lp-PLA2， HCY and combined diagnosis of ischemic stroke were 0.768，0.823，0.855 and 0.879， respectively （P＜ 0.01）. The area under ROC curve of serum PLR， Lp-PLA2 and HCY for short-term prognosis were 0.803，0.796 and 0.788 respectively. Conclusions The serum levels of PLR， Lp-PLA2 and HCY increased significantly in patients with ischemic stroke. The combined detection has high diagnostic efficiency， better clinical prognosis evaluation value， which can be a biological index for early prediction of ischemic stroke.