This research strived to determine the effectiveness of reasoning and problem solving learning model and problem-based learning model on problem solving skills in immune system material by the students in grade XI in SMA N 5 Semarang. It was in form of quasi-experimental research. For the variables, this research had reasoning and problemsolving learning model and problem-based learning model as the independent variables, and problem solving skills as the dependent variable. In terms of sample, this research used probability sampling technique so that all students deserved to be the research objects. The samples came from the students of Natural Science (IPA) 10 in grade XI as the control class, while as the experimental class, there were students of IPA 8 in grade XI, and students of IPA 9 in grade XI. Their data were collected using portfolio, observation, and documentation. Further, the researchers performed data analysis using normality test through chi square formula, homogeneity test with Bartlett test, and average difference test with t-test. The findings of the research showed significant differences, namely the experimental class 1 gained 85, the experimental class 2 gained 85 and the control class gained 82. These indicate that the reasoning and problem-solving learning model and problem-based learning model have some effects on the problem solving skills in immune system material by the students in grade XI in SMA N 5 Semarang.