纯CSS解决方案可在此jsfiddle中找到
HTML语言

<div class="wrap">
    <div class="flex-c">
        <div class="flex-i big"></div>
        <div class="flex-i red"></div>
        <div class="flex-i big green"></div>
        <div class="flex-i green"></div>
        <div class="flex-i red"></div>
        <div class="flex-i blue"></div>
        <div class="flex-i green"></div>
        <div class="flex-i red"></div>
        <div class="flex-i blue"></div>
        <div class="flex-i green"></div>
        <div class="flex-i red"></div>
        <div class="flex-i blue"></div>
        <div class="flex-i green"></div>
        <div class="flex-i red"></div>
        <div class="flex-i blue"></div>
        <div class="flex-i green"></div>
        <div class="flex-i red"></div>
        <div class="flex-i blue"></div>
        <div class="flex-i green"></div>
        <div class="flex-i red"></div>
        <div class="flex-i blue"></div>
    </div>
</div>

CSS

.flex-c:after {
    content: '';
    display: table;
    clear: both;
}
.flex-i.red { background-color: red; }
.flex-i.blue {background-color: blue; }
.flex-i.green {background-color: green;}
.flex-i {
    transform: rotate(90deg) scaleY(-1);
    height: 100px;
    width: 100px;
    background-color: gray;
    margin: 0 10px 10px 0;
    float: left;
}
.flex-i:after,
.flex-i.big:before {
    content: '';
    height: 100px;
    width: 100px;
    left: 110px;
    top: 0;
    position: absolute;
    background-color: pink;
}

.flex-i.big:after {
    left: 220px;
}
.flex-i.big:before {
    left: 220px;
    bottom: 0;
    top: auto;
}

.big {
    width: 210px;
    height: 210px;
}

另外
使用Isotopes JS masonry layout等库可能会使您受益
它可以帮助您生成已显示的布局样式。
下面是一个工作示例。
HTML语言

<div id="container">
    <div class="item"></div>
    <div class="item w2"></div>
    <div class="item"></div>
    <div class="item w2"></div>
    <div class="item h2"></div>
    <div class="item"></div>
    <div class="item h2"></div>
    <div class="item w2 h2"></div>
    <div class="item"></div>
    <div class="item"></div>
    <div class="item h2"></div>
    <div class="item"></div>
    <div class="item"></div>
    <div class="item w2"></div>
    <div class="item h2"></div>
    <div class="item"></div>
    <div class="item h2"></div>
</div>

CSS

#container {
    border: 1px solid;
    padding: 7px;
}

.item {
    width: 60px;
    height: 60px;
    float: left;
    margin: 3px;
    background: #CCC;
}

.item.w2 {
    width: 130px;
}

.item.h2 {
    height: 130px;
}

JS -注意，必须将masonry应用于父元素，在本例中是container的id

$( function() {
    var $container = $('#container').masonry({
        itemSelector: '.item',
        columnWidth: 70
    });
});

查看jsFiddle here

看下面的代码：
第一个