With the continuous reform of education and the ongoing development of teaching methods by the Macao government, the teaching model of biology is also constantly evolving. The “5E” instructional model, proposed and developed by the Biological Sciences Curriculum Study (BSCS) in the United States, consists of a learning cycle divided into five phases: Engagement, Exploration, Explanation, Elaboration, and Evaluation. Each phase begins with the letter “E,” hence it named as the 5E teaching model. This model is currently widely applied in inquiry-based teaching across multiple countries. This article is a research study on practical teaching, where the researcher attempts to integrate information technology with the 5E learining method in an 8th Grade biology class. The aim is to explore whether the learning attitudes and academic performance of middle school students can be enhanced in the context of the 21st century. The focus of this study is on the chapter about the “Immune System,” selecting two parallel classes of 8th Grade students from a secondary school in Macao as research subjects. One class uses the 5E model, while the other teaching with traditional lecturing methods. Through Document Analysis, equivalent-group design, and questionnaire surveys and lesson plan based on 5E model, statistical software SPSS 22 is used to analyze the data regarding students’ biology learning attitudes and academic performance, thereby assessing the effectiveness of teaching using the 5E model and identifying issues encountered during the teaching process to provide targeted teaching strategies. The research findings indicate: (1) There is no significant difference in the learning attitudes and performance of students in the experimental class compared to the control class regarding the immune system unit. (2) There is no significant difference in the learning attitudes and performance of students in the experimental class before and after receiving 5E teaching. (3) For students with average academic performance, the experimental class shows significant differences in learning interest and strategies compared to the control class after undergoing 5E teaching. (4) Among students with average academic performance in the experimental group, there is a significant difference in learning interest after 5E teaching compared to before. (5) Students express high satisfaction with the teacher’s integration of information technology into the 5E teaching model, which can stimulate their interest in learning natural sciences.